spacer
spacer

PDBsum entry 1b5t

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1b5t
Jmol
Contents
Protein chains
275 a.a. *
Ligands
FAD ×3
Metals
_HG ×3
Waters ×184
* Residue conservation analysis
PDB id:
1b5t
Name: Oxidoreductase
Title: Escherichia coli methylenetetrahydrofolate reductase
Structure: Protein (methylenetetrahydrofolate reductase). Chain: a, b, c. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: metf. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.212     R-free:   0.263
Authors: B.D.Guenther,C.A.Sheppard,P.Tran,R.Rozen,R.G.Matthews, M.L.Ludwig
Key ref:
B.D.Guenther et al. (1999). The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol, 6, 359-365. PubMed id: 10201405 DOI: 10.1038/7594
Date:
07-Jan-99     Release date:   20-Jan-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AEZ1  (METF_ECOLI) -  5,10-methylenetetrahydrofolate reductase
Seq:
Struc:
296 a.a.
275 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.5.1.20  - Methylenetetrahydrofolate reductase (NAD(P)H).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Folate Coenzymes
      Reaction: 5-methyltetrahydrofolate + NAD(P)(+) = 5,10-methylenetetrahydrofolate + NAD(P)H
5-methyltetrahydrofolate
+ NAD(P)(+)
= 5,10-methylenetetrahydrofolate
+ NAD(P)H
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     tetrahydrofolate interconversion   8 terms 
  Biochemical function     FAD binding     3 terms  

 

 
    reference    
 
 
DOI no: 10.1038/7594 Nat Struct Biol 6:359-365 (1999)
PubMed id: 10201405  
 
 
The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia.
B.D.Guenther, C.A.Sheppard, P.Tran, R.Rozen, R.G.Matthews, M.L.Ludwig.
 
  ABSTRACT  
 
Elevated plasma homocysteine levels are associated with increased risk for cardiovascular disease and neural tube defects in humans. Folate treatment decreases homocysteine levels and dramatically reduces the incidence of neural tube defects. The flavoprotein methylenetetrahydrofolate reductase (MTHFR) is a likely target for these actions of folate. The most common genetic cause of mildly elevated plasma homocysteine in humans is the MTHFR polymorphism A222V (base change C677-->T). The X-ray analysis of E. coli MTHFR, reported here, provides a model for the catalytic domain that is shared by all MTHFRs. This domain is a beta8alpha8 barrel that binds FAD in a novel fashion. Ala 177, corresponding to Ala 222 in human MTHFR, is near the bottom of the barrel and distant from the FAD. The mutation A177V does not affect Km or k(cat) but instead increases the propensity for bacterial MTHFR to lose its essential flavin cofactor. Folate derivatives protect wild-type and mutant E. coli enzymes against flavin loss, and protect human MTHFR and the A222V mutant against thermal inactivation, suggesting a mechanism by which folate treatment reduces homocysteine levels.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. The structure of E. coli MTHFR. a, A view along the axis of the [8] [8] barrel looking toward the C-terminal ends of the −strands^37. FAD is drawn in ball-and-stick mode. Helix 5, which precedes the site corresponding to the human A arrow V polymorphism, is colored red in this and succeeding figures. b, A view perpendicular to the barrel axis and toward the si face of the flavin ring, showing the truncation of strand 8 and helix 8 and the resulting groove in which methylenetetrahydrofolate is expected to bind. Ala 177, the site of the Ala arrow Val mutation, is drawn with gray dot surfaces, and is at the rear of the barrel. c, A stereo drawing of the chain fold from approximately the same perspective as in ( a).
Figure 6.
Figure 6. a, The location and environment of the Ala 177 that corresponds to the site of the A arrow V polymorphism in human MTHFR. The view is approximately perpendicular to the barrel axis and oriented to show helix 5 and its neighboring barrel strands. Black dot surfaces trace the helix backbone from 171 to 176; red surfaces represent the volume of alanine at position 177, and green surfaces a valine substituted at position 177 which clearly overlaps the helix backbone. The side chains of Lys 172, Asn 168, and Asp 165 that interact with FAD are drawn in ball-and-stick mode with carbons in cyan. b, The tetramer of E. coli MTHFR, viewed down the local two-fold axis. The asymmetric unit of the monoclinic cell contains the three chains A, B, and C; the fourth chain of the tetramer (A') is related to A by a crystallographic two-fold axis. The C and B subunits can be superimposed on chains A and A' by a local dyad (perpendicular to the page) that is inclined by ~53° to the crystallographic dyad along axis y. This local dyad is the only symmetry operator that relates the chains of the tetramer to one another. Interfaces A−A' and B−C are formed by symmetric interactions between helices 7c, 7b, and 8. In contrast, the A and B (or C and A') chains are not related by a simple rotation of 360/n^O; the B chain is superimposed on the A chain by a rotation of 108° and a translation of ~7 Å. Helix 5, which may be critical in mediating the effects of mutation at position 177, is drawn in red, and Ala 177 is white and surrounded by dot surfaces. The figure was prepared using the program RIBBONS^37.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 359-365) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21281325 M.A.Cleves, C.A.Hobbs, W.Zhao, P.A.Krakowiak, and S.L.Macleod (2011).
Association between selected folate pathway polymorphisms and nonsyndromic limb reduction defects: a case-parental analysis.
  Paediatr Perinat Epidemiol, 25, 124-134.  
19954568 C.P.Wilson, H.McNulty, J.M.Scott, J.J.Strain, and M.Ward (2010).
Postgraduate Symposium: The MTHFR C677T polymorphism, B-vitamins and blood pressure.
  Proc Nutr Soc, 69, 156-165.  
20502473 I.Johansson, B.Van Guelpen, J.Hultdin, M.Johansson, G.Hallmans, and P.Stattin (2010).
Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification.
  Eur J Clin Nutr, 64, 905-913.  
20236116 R.Urreizti, A.A.Moya-García, A.Pino-Ángeles, M.Cozar, A.Langkilde, U.Fanhoe, C.Esteves, J.Arribas, M.A.Vilaseca, B.Pérez-Dueñas, M.Pineda, V.González, R.Artuch, A.Baldellou, L.Vilarinho, B.Fowler, A.Ribes, F.Sánchez-Jiménez, D.Grinberg, and S.Balcells (2010).
Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency.
  Clin Genet, 78, 441-448.  
19174578 A.Schatzkin, C.C.Abnet, A.J.Cross, M.Gunter, R.Pfeiffer, M.Gail, U.Lim, and G.Davey-Smith (2009).
Mendelian randomization: how it can--and cannot--help confirm causal relations between nutrition and cancer.
  Cancer Prev Res (Phila), 2, 104-113.  
19930673 F.Jin, L.S.Qu, and X.Z.Shen (2009).
Association between the methylenetetrahydrofolate reductase C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis.
  Diagn Pathol, 4, 39.  
19123462 K.J.Sohn, H.Jang, M.Campan, D.J.Weisenberger, J.Dickhout, Y.C.Wang, R.C.Cho, Z.Yates, M.Lucock, E.P.Chiang, R.C.Austin, S.W.Choi, P.W.Laird, and Y.I.Kim (2009).
The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification.
  Int J Cancer, 124, 1999-2005.  
19610625 M.N.Lee, D.Takawira, A.P.Nikolova, D.P.Ballou, V.C.Furtado, N.L.Phung, B.R.Still, M.K.Thorstad, J.J.Tanner, and E.E.Trimmer (2009).
Functional role for the conformationally mobile phenylalanine 223 in the reaction of methylenetetrahydrofolate reductase from Escherichia coli.
  Biochemistry, 48, 7673-7685.
PDB codes: 3fst 3fsu
19609317 N.Fodil-Cornu, N.Kozij, Q.Wu, R.Rozen, and S.M.Vidal (2009).
Methylenetetrahydrofolate reductase (MTHFR) deficiency enhances resistance against cytomegalovirus infection.
  Genes Immun, 10, 662-666.  
19596855 R.G.Matthews (2009).
A love affair with vitamins.
  J Biol Chem, 284, 26217-26228.  
19450180 Y.I.Kim (2009).
Role of the MTHFR polymorphisms in cancer risk modification and treatment.
  Future Oncol, 5, 523-542.  
18850188 E.Mocchegiani, and M.Malavolta (2008).
Zinc-gene interaction related to inflammatory/immune response in ageing.
  Genes Nutr, 3, 61-75.  
  18670064 E.Trabetti (2008).
Homocysteine, MTHFR gene polymorphisms, and cardio-cerebrovascular risk.
  J Appl Genet, 49, 267-282.  
18708408 J.C.Figueiredo, A.J.Levine, M.V.Grau, O.Midttun, P.M.Ueland, D.J.Ahnen, E.L.Barry, S.Tsang, D.Munroe, I.Ali, R.W.Haile, R.S.Sandler, and J.A.Baron (2008).
Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.
  Cancer Epidemiol Biomarkers Prev, 17, 2136-2145.  
18053312 L.Sharp, J.Little, N.T.Brockton, S.C.Cotton, L.F.Masson, N.E.Haites, and J.Cassidy (2008).
Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake.
  Br J Nutr, 99, 379-389.  
18074111 M.A.Alam, S.A.Husain, R.Narang, S.S.Chauhan, M.Kabra, and S.Vasisht (2008).
Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease.
  Mol Cell Biochem, 310, 111-117.  
18446861 M.L.Martínez-Frías (2008).
The biochemical structure and function of methylenetetrahydrofolate reductase provide the rationale to interpret the epidemiological results on the risk for infants with Down syndrome.
  Am J Med Genet A, 146, 1477-1482.  
18523009 N.J.Marini, J.Gin, J.Ziegle, K.H.Keho, D.Ginzinger, D.A.Gilbert, and J.Rine (2008).
The prevalence of folate-remedial MTHFR enzyme variants in humans.
  Proc Natl Acad Sci U S A, 105, 8055-8060.  
17725378 N.Yazdanpanah, A.G.Uitterlinden, M.C.Zillikens, M.Jhamai, F.Rivadeneira, A.Hofman, R.de Jonge, J.Lindemans, H.A.Pols, and J.B.van Meurs (2008).
Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.
  J Bone Miner Res, 23, 86-94.  
18266839 P.R.Solomon, G.S.Selvam, and G.Shanmugam (2008).
Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians.
  Oral Dis, 14, 633-639.  
18801467 S.W.Ragsdale, and E.Pierce (2008).
Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.
  Biochim Biophys Acta, 1784, 1873-1898.  
17712558 A.K.Siraj, M.Ibrahim, M.Al-Rasheed, R.Bu, P.Bavi, Z.Jehan, J.Abubaker, W.Murad, F.Al-Dayel, A.Ezzat, H.El-Solh, S.Uddin, and K.Al-Kuraya (2007).
Genetic polymorphisms of methylenetetrahydrofolate reductase and promoter methylation of MGMT and FHIT genes in diffuse large B cell lymphoma risk in Middle East.
  Ann Hematol, 86, 887-895.  
17115185 A.Ulvik, P.M.Ueland, A.Fredriksen, K.Meyer, S.E.Vollset, G.Hoff, and J.Schneede (2007).
Functional inference of the methylenetetrahydrofolate reductase 677C > T and 1298A > C polymorphisms from a large-scale epidemiological study.
  Hum Genet, 121, 57-64.  
17303386 C.J.Piyathilake, M.Azrad, M.Macaluso, G.L.Johanning, P.E.Cornwell, E.E.Partridge, and D.C.Heimburger (2007).
Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status.
  Nutrition, 23, 229-235.  
17672887 G.Mayr, F.S.Domingues, and P.Lackner (2007).
Comparative analysis of protein structure alignments.
  BMC Struct Biol, 7, 50.  
17436239 S.Hustad, ..Midttun, J.Schneede, S.E.Vollset, T.Grotmol, and P.M.Ueland (2007).
The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism.
  Am J Hum Genet, 80, 846-855.  
17695371 S.Vakili, and M.A.Caudill (2007).
Personalized nutrition: nutritional genomics as a potential tool for targeted medical nutrition therapy.
  Nutr Rev, 65, 301-315.  
  17119116 U.Lim, S.S.Wang, P.Hartge, W.Cozen, L.E.Kelemen, S.Chanock, S.Davis, A.Blair, M.Schenk, N.Rothman, and Q.Lan (2007).
Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.
  Blood, 109, 3050-3059.  
16924261 H.J.Blom, G.M.Shaw, M.den Heijer, and R.H.Finnell (2006).
Neural tube defects and folate: case far from closed.
  Nat Rev Neurosci, 7, 724-731.  
16172608 J.W.Muntjewerff, R.S.Kahn, H.J.Blom, and M.den Heijer (2006).
Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis.
  Mol Psychiatry, 11, 143-149.  
16518429 N.Murphy, M.Diviney, J.Szer, P.Bardy, A.Grigg, R.Hoyt, B.King, L.Macgregor, R.Holdsworth, J.McCluskey, and B.D.Tait (2006).
Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate.
  Bone Marrow Transplant, 37, 773-779.  
16933051 N.T.Brockton (2006).
Localized depletion: the key to colorectal cancer risk mediated by MTHFR genotype and folate?
  Cancer Causes Control, 17, 1005-1016.  
16601863 R.Castro, I.Rivera, H.J.Blom, C.Jakobs, and I.Tavares de Almeida (2006).
Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview.
  J Inherit Metab Dis, 29, 3.  
16605249 R.Pejchal, E.Campbell, B.D.Guenther, B.W.Lennon, R.G.Matthews, and M.L.Ludwig (2006).
Structural perturbations in the Ala --> Val polymorphism of methylenetetrahydrofolate reductase: how binding of folates may protect against inactivation.
  Biochemistry, 45, 4808-4818.
PDB codes: 2fmn 2fmo
17032644 T.J.Vickers, G.Orsomando, R.D.de la Garza, D.A.Scott, S.O.Kang, A.D.Hanson, and S.M.Beverley (2006).
Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence.
  J Biol Chem, 281, 38150-38158.  
16207145 K.Robien, A.Boynton, and C.M.Ulrich (2005).
Pharmacogenetics of folate-related drug targets in cancer treatment.
  Pharmacogenomics, 6, 673-689.  
16024724 K.Yamada, J.R.Strahler, P.C.Andrews, and R.G.Matthews (2005).
Regulation of human methylenetetrahydrofolate reductase by phosphorylation.
  Proc Natl Acad Sci U S A, 102, 10454-10459.  
15735347 L.Lehtiö, I.Fabrichniy, T.Hansen, P.Schönheit, and A.Goldman (2005).
Unusual twinning in an acetyl coenzyme A synthetase (ADP-forming) from Pyrococcus furiosus.
  Acta Crystallogr D Biol Crystallogr, 61, 350-354.  
15738964 M.Lucock, and Z.Yates (2005).
Folic acid - vitamin and panacea or genetic time bomb?
  Nat Rev Genet, 6, 235-240.  
15548532 P.Gin, and C.F.Clarke (2005).
Genetic evidence for a multi-subunit complex in coenzyme Q biosynthesis in yeast and the role of the Coq1 hexaprenyl diphosphate synthase.
  J Biol Chem, 280, 2676-2681.  
15617551 R.Dodelson de Kremer, and C.Grosso (2005).
Maternal mutation 677C > T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring.
  Clin Genet, 67, 69-80.  
16049018 R.H.van den Heuvel, N.Tahallah, N.M.Kamerbeek, M.W.Fraaije, W.J.van Berkel, D.B.Janssen, and A.J.Heck (2005).
Coenzyme binding during catalysis is beneficial for the stability of 4-hydroxyacetophenone monooxygenase.
  J Biol Chem, 280, 32115-32121.  
15937276 S.W.Aufhammer, E.Warkentin, U.Ermler, C.H.Hagemeier, R.K.Thauer, and S.Shima (2005).
Crystal structure of methylenetetrahydromethanopterin reductase (Mer) in complex with coenzyme F420: Architecture of the F420/FMN binding site of enzymes within the nonprolyl cis-peptide containing bacterial luciferase family.
  Protein Sci, 14, 1840-1849.
PDB code: 1z69
16351505 T.Otani, M.Iwasaki, T.Hanaoka, M.Kobayashi, J.Ishihara, S.Natsukawa, K.Shaura, Y.Koizumi, Y.Kasuga, K.Yoshimura, T.Yoshida, and S.Tsugane (2005).
Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan.
  Nutr Cancer, 53, 42-50.  
16370225 Y.I.Kim (2005).
5,10-Methylenetetrahydrofolate reductase polymorphisms and pharmacogenetics: a new role of single nucleotide polymorphisms in the folate metabolic pathway in human health and disease.
  Nutr Rev, 63, 398-407.  
15166809 A.M.Molloy (2004).
Folate and homocysteine interrelationships including genetics of the relevant enzymes.
  Curr Opin Lipidol, 15, 49-57.  
15103708 S.J.James (2004).
Maternal metabolic phenotype and risk of Down syndrome: beyond genetics.
  Am J Med Genet A, 127, 1-4.  
15016352 S.W.Aufhammer, E.Warkentin, H.Berk, S.Shima, R.K.Thauer, and U.Ermler (2004).
Coenzyme binding in F420-dependent secondary alcohol dehydrogenase, a member of the bacterial luciferase family.
  Structure, 12, 361-370.
PDB code: 1rhc
14622288 M.H.Hefti, J.Vervoort, and W.J.van Berkel (2003).
Deflavination and reconstitution of flavoproteins.
  Eur J Biochem, 270, 4227-4242.  
12747601 W.Herrmann, R.Obeid, H.Schorr, W.Zarzour, and J.Geisel (2003).
Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and the B-vitamins: a facet of nature-nurture interplay.
  Clin Chem Lab Med, 41, 547-553.  
12514740 Y.H.Lee, S.Nadaraia, D.Gu, D.F.Becker, and J.J.Tanner (2003).
Structure of the proline dehydrogenase domain of the multifunctional PutA flavoprotein.
  Nat Struct Biol, 10, 109-114.
PDB codes: 1k87 4o8a
12400059 C.A.Hobbs, M.A.Cleves, R.M.Lauer, T.L.Burns, and S.J.James (2002).
Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage.
  Am J Med Genet, 113, 9.  
11929966 S.Friso, S.W.Choi, D.Girelli, J.B.Mason, G.G.Dolnikowski, P.J.Bagley, O.Olivieri, P.F.Jacques, I.H.Rosenberg, R.Corrocher, and J.Selhub (2002).
A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status.
  Proc Natl Acad Sci U S A, 99, 5606-5611.  
11729203 S.Roje, S.Y.Chan, F.Kaplan, R.K.Raymond, D.W.Horne, D.R.Appling, and A.D.Hanson (2002).
Metabolic engineering in yeast demonstrates that S-adenosylmethionine controls flux through the methylenetetrahydrofolate reductase reaction in vivo.
  J Biol Chem, 277, 4056-4061.  
12138370 T.B.Domagala, L.Adamek, E.Nizankowska, M.Sanak, and A.Szczeklik (2002).
Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease.
  Blood Coagul Fibrinolysis, 13, 423-431.  
11395038 I.S.Weisberg, P.F.Jacques, J.Selhub, A.G.Bostom, Z.Chen, R.Curtis Ellison, J.H.Eckfeldt, and R.Rozen (2001).
The 1298A-->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine.
  Atherosclerosis, 156, 409-415.  
11752418 J.M.Scott (2001).
Genetic diversity and disease: opportunities and challenge.
  Proc Natl Acad Sci U S A, 98, 14754-14756.  
11742092 K.Yamada, Z.Chen, R.Rozen, and R.G.Matthews (2001).
Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase.
  Proc Natl Acad Sci U S A, 98, 14853-14858.  
11514662 O.Dym, and D.Eisenberg (2001).
Sequence-structure analysis of FAD-containing proteins.
  Protein Sci, 10, 1712-1728.  
11282420 P.M.Ueland, S.Hustad, J.Schneede, H.Refsum, and S.E.Vollset (2001).
Biological and clinical implications of the MTHFR C677T polymorphism.
  Trends Pharmacol Sci, 22, 195-201.  
11085827 I.S.Young, and J.V.Woodside (2000).
Folate and homocysteine.
  Curr Opin Clin Nutr Metab Care, 3, 427-432.  
10986435 N.M.van der Put, and H.J.Blom (2000).
Neural tube defects and a disturbed folate dependent homocysteine metabolism.
  Eur J Obstet Gynecol Reprod Biol, 92, 57-61.  
11024273 P.Bourhy, and I.Saint Girons (2000).
Localization of the Leptospira interrogans metF gene on the CII secondary chromosome.
  FEMS Microbiol Lett, 191, 259-263.  
10923034 P.Goyette, and R.Rozen (2000).
The thermolabile variant 677C-->T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase.
  Hum Mutat, 16, 132-138.  
10679944 S.Sibani, B.Christensen, E.O'Ferrall, I.Saadi, F.Hiou-Tim, D.S.Rosenblatt, and R.Rozen (2000).
Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria.
  Hum Mutat, 15, 280-287.  
  10548046 J.J.Barycki, L.K.O'Brien, J.J.Birktoft, A.W.Strauss, and L.J.Banaszak (1999).
Pig heart short chain L-3-hydroxyacyl-CoA dehydrogenase revisited: sequence analysis and crystal structure determination.
  Protein Sci, 8, 2010-2018.
PDB code: 3hdh
10593891 S.Roje, H.Wang, S.D.McNeil, R.K.Raymond, D.R.Appling, Y.Shachar-Hill, H.J.Bohnert, and A.D.Hanson (1999).
Isolation, characterization, and functional expression of cDNAs encoding NADH-dependent methylenetetrahydrofolate reductase from higher plants.
  J Biol Chem, 274, 36089-36096.  
10551815 X.Shan, L.Wang, R.Hoffmaster, and W.D.Kruger (1999).
Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae.
  J Biol Chem, 274, 32613-32618.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.